Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • Allergy (Apr 2019)
    • Biology of familial cancer predisposition syndromes (Feb 2019)
    • Mitochondrial dysfunction in disease (Aug 2018)
    • Lipid mediators of disease (Jul 2018)
    • Cellular senescence in human disease (Apr 2018)
    • View all review series...
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Scientific Show Stoppers
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication
Top
  • View PDF
  • Download citation information
  • Send a letter
  • Terms of use
  • Standard abbreviations
  • Article usage
  • Citations to this article
  • Share this article
  • Need Help? E-mail the JCI
  • Top
  • Footnotes
  • Version history

Advertisement

Expression of concern Free access | 10.1172/JCI122301

ATP11B mediates platinum resistance in ovarian cancer

Myrthala Moreno-Smith, J.B. Halder, Paul S. Meltzer, Tamas A. Gonda, Lingegowda S. Mangala, Rajesha Rupaimoole, Chunhua Lu, Archana S. Nagaraja, Kshipra M. Gharpure, Yu Kang, Cristian Rodriguez-Aguayo, Pablo E. Vivas-Mejia, Behrouz Zand, Rosemarie Schmandt, Hua Wang, Robert R. Langley, Nicholas B. Jennings, Cristina Ivan, Jeremy E. Coffin, Guillermo N. Armaiz, Justin Bottsford-Miller, Sang Bae Kim, Margaret S. Halleck, Mary J.C. Hendrix, William Bornman, Menashe Bar-Eli, Ju-Seog Lee, Zahid H. Siddik, Gabriel Lopez-Berestein, and Anil K. Sood

Find articles by Moreno-Smith, M. in: JCI | PubMed | Google Scholar

Find articles by Halder, J. in: JCI | PubMed | Google Scholar

Find articles by Meltzer, P. in: JCI | PubMed | Google Scholar

Find articles by Gonda, T. in: JCI | PubMed | Google Scholar

Find articles by Mangala, L. in: JCI | PubMed | Google Scholar

Find articles by Rupaimoole, R. in: JCI | PubMed | Google Scholar

Find articles by Lu, C. in: JCI | PubMed | Google Scholar

Find articles by Nagaraja, A. in: JCI | PubMed | Google Scholar

Find articles by Gharpure, K. in: JCI | PubMed | Google Scholar

Find articles by Kang, Y. in: JCI | PubMed | Google Scholar

Find articles by Rodriguez-Aguayo, C. in: JCI | PubMed | Google Scholar

Find articles by Vivas-Mejia, P. in: JCI | PubMed | Google Scholar

Find articles by Zand, B. in: JCI | PubMed | Google Scholar

Find articles by Schmandt, R. in: JCI | PubMed | Google Scholar

Find articles by Wang, H. in: JCI | PubMed | Google Scholar

Find articles by Langley, R. in: JCI | PubMed | Google Scholar

Find articles by Jennings, N. in: JCI | PubMed | Google Scholar

Find articles by Ivan, C. in: JCI | PubMed | Google Scholar

Find articles by Coffin, J. in: JCI | PubMed | Google Scholar

Find articles by Armaiz, G. in: JCI | PubMed | Google Scholar

Find articles by Bottsford-Miller, J. in: JCI | PubMed | Google Scholar

Find articles by Kim, S. in: JCI | PubMed | Google Scholar

Find articles by Halleck, M. in: JCI | PubMed | Google Scholar

Find articles by Hendrix, M. in: JCI | PubMed | Google Scholar

Find articles by Bornman, W. in: JCI | PubMed | Google Scholar

Find articles by Bar-Eli, M. in: JCI | PubMed | Google Scholar

Find articles by Lee, J. in: JCI | PubMed | Google Scholar

Find articles by Siddik, Z. in: JCI | PubMed | Google Scholar

Find articles by Lopez-Berestein, G. in: JCI | PubMed | Google Scholar

Find articles by Sood, A. in: JCI | PubMed | Google Scholar

First published May 29, 2018 - More info

Published in Volume 128, Issue 7 on July 2, 2018
J Clin Invest. 2018;128(7):3199–3199. https://doi.org/10.1172/JCI122301.
Copyright © 2018, American Society for Clinical Investigation
First published May 29, 2018 - Version history

Related article:

ATP11B mediates platinum resistance in ovarian cancer
Myrthala Moreno-Smith, … , Gabriel Lopez-Berestein, Anil K. Sood
Myrthala Moreno-Smith, … , Gabriel Lopez-Berestein, Anil K. Sood
Category: Research Article

ATP11B mediates platinum resistance in ovarian cancer

  • Text
  • PDF
Abstract

Platinum compounds display clinical activity against a wide variety of solid tumors; however, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. We found that ATP11B expression was correlated with higher tumor grade in human ovarian cancer samples and with cisplatin resistance in human ovarian cancer cell lines. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-targeted siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux kinetics indicated that ATP11B enhances the export of cisplatin from cells. The colocalization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins, such as syntaxin-6 (STX6) and vesicular-associated membrane protein 4 (VAMP4), strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, inhibition of ATP11B expression could serve as a therapeutic strategy to overcome cisplatin resistance.

Authors

Myrthala Moreno-Smith, J.B. Halder, Paul S. Meltzer, Tamas A. Gonda, Lingegowda S. Mangala, Rajesha Rupaimoole, Chunhua Lu, Archana S. Nagaraja, Kshipra M. Gharpure, Yu Kang, Cristian Rodriguez-Aguayo, Pablo E. Vivas-Mejia, Behrouz Zand, Rosemarie Schmandt, Hua Wang, Robert R. Langley, Nicholas B. Jennings, Cristina Ivan, Jeremy E. Coffin, Guillermo N. Armaiz, Justin Bottsford-Miller, Sang Bae Kim, Margaret S. Halleck, Mary J.C. Hendrix, William Bornman, Menashe Bar-Eli, Ju-Seog Lee, Zahid H. Siddik, Gabriel Lopez-Berestein, Anil K. Sood

×

Original citation: J Clin Invest. 2013;123(5):2119–2130. https://doi.org/10.1172/JCI65425

Citation for this expression of concern: J Clin Invest. 2018;128(7):3199. https://doi.org/10.1172/JCI122301

The Editors recently became aware that Figure 3B appears to use a set of images that were previously published in a 2009 Clinical Cancer Research paper with different sample labels (doi: 10.1158/1078-0432.CCR-08-2306). Additionally, the empty liposome and control siRNA PCNA–stained panels appear to be the same. The Editorial Board is pursuing further investigation of this matter, and we will inform our readers of the outcome when the investigation is complete.

Footnotes

See the related article at ATP11B mediates platinum resistance in ovarian cancer.

Version history
  • Version 1 (May 29, 2018): Electronic publication
  • Version 2 (July 2, 2018): Print issue publication

Article tools

  • View PDF
  • Download citation information
  • Send a letter
  • Terms of use
  • Standard abbreviations
  • Article usage
  • Citations to this article
  • Share this article
  • Need Help? E-mail the JCI

Go to:

  • Top
  • Footnotes
  • Version history
Advertisement
Advertisement
Follow JCI:
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts